1. Field of the Invention
The present invention relates to the field of treating or preventing tissue deterioration, injury or damage due to congestive heart failure.
2. Description of the Background Art
Congestive heart failure (CHF) disease is manifested in an imbalance in heart pump function in which the heart fails to maintain the circulation of blood adequately. The most severe manifestation of CHF, pulmonary edema, develops when this imbalance causes an increase in lung fluid secondary to leakage from pulmonary capillaries into the interstitium and alveoli of the lung.
CHF can be categorized as forward or backward ventricular failure. Backward failures is secondary to elevated systemic venous pressure, while left ventricular failure is secondary to reduced forward flow into the aorta and systemic circulation. Furthermore, heart failure can be subdivided into systolic and diastolic dysfunction. Systolic dysfunction is characterized by a dilated left ventricle with impaired contractility, while diastolic dysfunction occurs in a normal or intact left ventricle with impaired ability to relax and receive as well as eject blood.
The New York Heart Association's functional classification of CHF is one of the most useful. Class I describes a patient who is not limited with normal physical activity by symptoms. Class II occurs when ordinary physical activity results in fatigue, dyspnea, or other symptoms. Class III is characterized by a marked limitation in normal physical activity. Class IV is defined by symptoms at rest or with any physical activity.
CHF is summarized best as an imbalance in Starling forces or an imbalance in the degree of end-diastolic fiber stretch proportional to the systolic mechanical work expended in an ensuing contraction. This imbalance may be characterized as a malfunction between the mechanisms that keep the interstitium and alveoli dry and the opposing forces that are responsible for fluid transfer to the interstitium.
Maintenance of plasma oncotic pressure (generally about 25 mm Hg) higher than pulmonary capillary pressure (about 7-12 mm Hg), maintenance of connective tissue and cellular barriers relatively impermeable to plasma proteins, and maintenance of an extensive lymphatic system are the mechanisms that keep the interstitium and alveoli dry.
Opposing forces responsible for fluid transfer to the interstitium include pulmonary capillary pressure and plasma oncotic pressure. Under normal circumstances, when fluid is transferred into the lung interstitium with increased lymphatic flow, no increase in interstitial volume occurs. When the capacity of lymphatic drainage is exceeded, however, liquid accumulates in the interstitial spaces surrounding the bronchioles and lung vasculature, thus creating CHF. When increased fluid and pressure cause tracking into the interstitial space around the alveoli and disruption of alveolar membrane junctions, fluid floods the alveoli and leads to pulmonary edema.
In the U.S., more than 3 million people have CHF, and more than 400,000 new patients present yearly. Prevalence of CHF is 1-2% of the general population.
Approximately 30-40% of patients with CHF are hospitalized every year. CHF is the leading diagnosis-related group among hospitalized patients older than 65 years. The 5-year mortality rate after diagnosis was reported in 1971 as 60% in men and 45% in women. In 1991, data showed the 5-year mortality rate of CHF essentially remaining unchanged, with a median survival of 3.2 years for males and 5.4 years for females. This may be secondary to an aging U.S. population with declining mortality due to other diseases.
The most common cause of CHF death is progressive heart failure, but sudden death may account for up to 45% of all deaths. After auditing data on 4606 patients hospitalized with CHF between 1992-1993, the total in-hospital mortality rate was 19%, with 30% of deaths occurring from noncardiac causes.
There remains a need in the art for methods of treatment for treating, preventing, inhibiting or reducing tissue deterioration, injury or damage due to congestive heart failure.